Department of Psychiatry, Neurology, and Epidemiology and Biostatistics, University of California, San Francisco, CA, USA; San Francisco VA Medical Center, San Francisco, CA, USA.
Hope Center for Neurological Disorders and Knight Alzheimer Disease Research Center, Department of Neurology, Washington University School of Medicine, St Louis, MO, USA.
Lancet Neurol. 2019 Mar;18(3):307-318. doi: 10.1016/S1474-4422(18)30461-7. Epub 2019 Feb 12.
Dysfunction in 24-h circadian rhythms is a common occurrence in ageing adults; however, circadian rhythm disruptions are more severe in people with age-related neurodegenerative diseases, including Alzheimer's disease and related dementias, and Parkinson's disease. Manifestations of circadian rhythm disruptions differ according to the type and severity of neurodegenerative disease and, for some patients, occur before the onset of typical clinical symptoms of neurodegeneration. Evidence from preliminary studies suggest that circadian rhythm disruptions, in addition to being a symptom of neurodegeneration, might also be a potential risk factor for developing Alzheimer's disease and related dementias, and Parkinson's disease, although large, longitudinal studies are needed to confirm this relationship. The mechanistic link between circadian rhythms and neurodegeneration is still not fully understood, although proposed underlying pathways include alterations of protein homoeostasis and immune and inflammatory function. While preliminary clinical studies are promising, more studies of circadian rhythm disruptions and its mechanisms are required. Furthermore, clinical trials are needed to determine whether circadian interventions could prevent or delay the onset of neurodegenerative diseases.
24 小时昼夜节律功能障碍在老年人群中很常见；然而，昼夜节律紊乱在与年龄相关的神经退行性疾病患者中更为严重，包括阿尔茨海默病及相关痴呆症和帕金森病。昼夜节律紊乱的表现因神经退行性疾病的类型和严重程度而异，对于一些患者而言，其发生时间早于神经退行性变的典型临床症状出现之前。初步研究证据表明，昼夜节律紊乱除了是神经退行性变的症状之外，还可能是阿尔茨海默病及相关痴呆症和帕金森病的潜在风险因素，尽管需要进行大型纵向研究来证实这种关系。昼夜节律与神经退行性变之间的机制联系尚不完全清楚，尽管提出的潜在途径包括蛋白质动态平衡以及免疫和炎症功能的改变。虽然初步的临床研究很有前景，但仍需要更多关于昼夜节律紊乱及其机制的研究。此外，还需要开展临床试验来确定昼夜节律干预是否可以预防或延缓神经退行性疾病的发作。
